Beta-blocker management of refractory hemoptysis in cystic fibrosis: a novel treatment approach

Background/objective: Recurrent hemoptysis is a debilitating complication of cystic fibrosis (CF) and likely results from mucosal erosions into abnormal bronchial blood vessels due to chronic respiratory infection. We hypothesize that the use of beta-blockade will decrease mean arterial pressure resulting in lower bronchial artery blood flow and, subsequently, decrease the frequency and severity of hemoptysis, rate of hospitalizations, and usage of intravenous antibiotics. Methods: Retrospective chart review was performed on 12 CF patients with recurrent hemoptysis, aged 13–40 years old, along with a follow-up telephone survey to assess the effectiveness of beta-blockade for hemoptysis, tolerance of inhaled respiratory medications, activity tolerance, and potential adverse effects. A beta-blocker, specifically atenolol, was initiated in all subjects within 24 hours after experiencing recurrent hemoptysis episodes. Results: A majority of patients (72.7%) had complete cessation of hemoptysis. There were significant decreases in the frequency of hemoptysis ( p = 0.02) and the amount of hemoptysis ( p = 0.004). The rate of hospitalizations significantly decreased from 1.33 to 0.67 ( p = 0.05) after initiation of atenolol. There was a trend toward statistical significance in the reduction of intravenous antibiotics use ( p = 0.08). No statistical difference was found when comparing the pre- and post-treatment means of forced expiratory volume in 1-second ( p = 0.59). Very minimal adverse effects were observed with only one patient reporting intermittent facial flushing. Conclusion: Beta-blockade, particularly with atenolol, appears to successfully treat, if not resolve, recurrent hemoptysis refractory to conservative therapy in CF. Beta-blocker therapy appears to maintain an effective safety profile in CF

Beta-blocker management of refractory hemoptysis in cystic fibrosis: a novel treatment approach.

Background/objective: Recurrent hemoptysis is a debilitating complication of cystic fibrosis (CF) and likely results from mucosal erosions into abnormal bronchial blood vessels due to chronic respiratory infection. We hypothesize that the use of beta-blockade will decrease mean arterial pressure resulting in lower bronchial artery blood flow and, subsequently, decrease the frequency and severity of hemoptysis, rate of hospitalizations, and usage of intravenous antibiotics.MethodsRetrospective chart review was performed on 12 CF patients with recurrent hemoptysis, aged 13-40 years old, along with a follow-up telephone survey to assess the effectiveness of beta-blockade for hemoptysis, tolerance of inhaled respiratory medications, activity tolerance, and potential adverse effects. A beta-blocker, specifically atenolol, was initiated in all subjects within 24 hours after experiencing recurrent hemoptysis episodes.ResultsA majority of patients (72.7%) had complete cessation of hemoptysis. There were significant decreases in the frequency of hemoptysis (p = 0.02) and the amount of hemoptysis (p = 0.004). The rate of hospitalizations significantly decreased from 1.33 to 0.67 (p = 0.05) after initiation of atenolol. There was a trend toward statistical significance in the reduction of intravenous antibiotics use (p = 0.08). No statistical difference was found when comparing the pre- and post-treatment means of forced expiratory volume in 1-second (p = 0.59). Very minimal adverse effects were observed with only one patient reporting intermittent facial flushing.ConclusionBeta-blockade, particularly with atenolol, appears to successfully treat, if not resolve, recurrent hemoptysis refractory to conservative therapy in CF. Beta-blocker therapy appears to maintain an effective safety profile in CF

Clinical significance of respiratory isolates for Mycobacterium abscessus complex from pediatric patients.

Mycobacterium abscessus complex is the most virulent of rapidly growing mycobacteria causing invasive lung disease. To better delineate clinical pediatric experience and outcomes with M. abscessus complex, we retrospectively gathered 5-year data on M. abscessus complex infection and outcomes in a large, hospital-based pediatric pulmonary center. Patients were selected from the database of the microbiology department at Miller Children's Hospital in Long Beach, CA. Patients had at least one positive pulmonary isolate for M. abscessus complex from February 2006 to May 2011. Treatment modality data were collected and successful therapy of disease was determined as clearance of M. abscessus complex infection after antibiotics proven by culture negative respiratory isolate within at least 12 months of therapy initiation. Two cystic fibrosis patients with M. abscessus complex were identified, one with failed therapy and the other with stable pulmonary status despite persistent isolation. One primary ciliary dyskinesia patient had successful clearance of M. abscessus complex, however is now growing M. avium intracellulare. A patient with no prior medical history was successfully treated with antimycobacterial therapy. Eleven patients with neuromuscular disorders had tracheal aspirates positive for M. abscessus complex. None were treated due to stable lung status and all but two had spontaneous clearance of the mycobacteria. The two remaining persist with sporadic isolation of M. abscessus complex without clinical significance. We concluded that patients with tracheostomy associated M. abscessus complex infections do not appear to require treatment and often have spontaneous resolution. Cystic fibrosis or primary ciliary dyskinesia patients may have clinical disease warranting treatment, but current antimycobacterial therapy has not proven to be completely successful. As M. abscessus complex gains prevalence, standardized guidelines for diagnosis and therapy are needed in the pediatric population. Multicenter cohort analysis is necessary to achieve such guidelines

Clinical significance of respiratory isolates for Mycobacterium abscessus complex from pediatric patients.

Mycobacterium abscessus complex is the most virulent of rapidly growing mycobacteria causing invasive lung disease. To better delineate clinical pediatric experience and outcomes with M. abscessus complex, we retrospectively gathered 5-year data on M. abscessus complex infection and outcomes in a large, hospital-based pediatric pulmonary center. Patients were selected from the database of the microbiology department at Miller Children's Hospital in Long Beach, CA. Patients had at least one positive pulmonary isolate for M. abscessus complex from February 2006 to May 2011. Treatment modality data were collected and successful therapy of disease was determined as clearance of M. abscessus complex infection after antibiotics proven by culture negative respiratory isolate within at least 12 months of therapy initiation. Two cystic fibrosis patients with M. abscessus complex were identified, one with failed therapy and the other with stable pulmonary status despite persistent isolation. One primary ciliary dyskinesia patient had successful clearance of M. abscessus complex, however is now growing M. avium intracellulare. A patient with no prior medical history was successfully treated with antimycobacterial therapy. Eleven patients with neuromuscular disorders had tracheal aspirates positive for M. abscessus complex. None were treated due to stable lung status and all but two had spontaneous clearance of the mycobacteria. The two remaining persist with sporadic isolation of M. abscessus complex without clinical significance. We concluded that patients with tracheostomy associated M. abscessus complex infections do not appear to require treatment and often have spontaneous resolution. Cystic fibrosis or primary ciliary dyskinesia patients may have clinical disease warranting treatment, but current antimycobacterial therapy has not proven to be completely successful. As M. abscessus complex gains prevalence, standardized guidelines for diagnosis and therapy are needed in the pediatric population. Multicenter cohort analysis is necessary to achieve such guidelines

CFTR gene variants, air pollution, and childhood asthma in a California Medicaid population

Carriers of the cystic fibrosis transmembrane conductance regulator (CFTR) gene ("carriers") have been found to have an increased risk of persistent asthma. However, it is unclear at what level of CFTR function this risk exists and whether it is modified by asthmogens, such as air pollution. We conducted a retrospective cohort study of children born in California between July 2007 and December 2013, linking CFTR genotype data from the California newborn screening program to Medicaid claims records through March 17, 2020 to identify asthma cases, and to air pollution data from CalEnviroScreen 3.0 to identify levels of particulate matter with diameter 2.5 microns or smaller (PM2.5 ). Log-binomial regression models for asthma risk were fitted, adjusting for race/ethnicity and sex. Compared to population controls, carriers had higher risk of asthma (adjusted risk ratio (aRR) = 1.29, 95% confidence interval (CI): 0.98, 1.69; p < 0.1). Other non-CF-causing variants on the second allele did not appear to further increase risk. Genotypes with the greatest asthma risk were F508del with an intron 10 T7 or (TG)11T5 in trans (aRR=1.52, 95% CI: 1.10, 2.12). This association was higher among children living in areas at or above (aRR = 1.80) versus below (aRR = 1.37) the current national air quality standard for PM2.5 , though this difference was not statistically significant (pinteraction  > 0.2). These results suggest carriers with CFTR functional levels between 25% and 45% of wildtype are at increased risk of asthma. Knowledge of CFTR genotype in asthmatics may be important to open new CFTR-related treatment options for these patients

The effect of α-mating factor secretion signal mutations on recombinant protein expression in Pichia pastoris.

The methylotrophic yeast, Pichia pastoris, has been genetically engineered to produce many heterologous proteins for industrial and research purposes. In order to secrete proteins for easier purification from the extracellular medium, the coding sequence of recombinant proteins is initially fused to the Saccharomyces cerevisiae α-mating factor secretion signal leader. Extensive site-directed mutagenesis of the prepro-region of the α-mating factor secretion signal sequence was performed in order to determine the effects of various deletions and substitutions on expression. Though some mutations clearly dampened protein expression, deletion of amino acids 57–70, corresponding to the predicted 3rd alpha helix of α-mating factor secretion signal, increased secretion of reporter proteins horseradish peroxidase and lipase at least 50% in small-scale cultures. These findings raise the possibility that the secretory efficiency of the leader can be further enhanced in the future